The proposal describes a series of experiments designed to elucidate the rules of mitochondrial transmission genetics and the mechanisms which underly those rules, using a combination of methods at the cellular and molecular levels. Yeast mitochondria will serve as a model system for investigation of general questions concerning the interaction of multiple genomes within a cell, the behavior of organelles during asexual and sexual reproduction, and mechanisms of mutation and recombination. These studies will provide background information for future studies of the role of organelle genomes in the development and evolution of organisms. Experiments will use petite and antibiotic resistant mutations in Saccharomyces cerevisiae. Experiments will probe the phenomena of vegetative segregation, biased transmission of genes, and uniparental inheritance common to most cases of organelle genetics; the origin of antibiotic-resistant mutant cells; and the unique (to yeast) phenomenon of petite mutagenesis. Mechanisms of organelle transmission genetics which will be explored include biased input of organelle DNA into the zygote; non-reciprocal recombination during random mating of DNA molecules and random drift of gene frequencies; preferential replication or enzymatic destruction of organelle DNA in the zygote; and factors affecting the mixing of mitochondria in zygotes and their transfer to buds. Major attention will be given to mtDNA metabolism in isolated zygotes exhibiting uniparental inheritance. We will also isolate and characterize a new class of mutants, showing loss of mitochondrial function, for use in probing mitochondrial genetic processes. BIBILIOGRAPHIC REFERENCES: Birky, C. William, Jr. and Skavaril, R.V. 1976 Maintenance of genetic homogeneity in systems with multiple genomes. Genet. Res. 27:249-265. Perlman, P.S., Birky, C.W., Jr., Demko, C.A. and Strausberg, R.L. 1976 Confirmations and exceptions to the phage analogy model: input bias, bud position effects, zygote heterogeneity, and uniparental inheritance. pp. 405-414. In Genetics and Biogenesis of Chloroplasts and Mitochondria (Bucher, Th., Neupert, W., Sebald, W. and Werner, S., eds.) Elsevier/North Holland Biomedical Press, Amsterdam.